A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205.

BACKGROUND: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown. METHODS: EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3-4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality. FINDINGS: 69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8-81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8-62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5-17.2) months and 27.1 (95% CI 22.6-64.3) months in arm A, and 8.0 (95% CI 7.2-21.9) months and 33.8 (95% CI 23.8-44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high. INTERPRETATION: EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

Survival difference between patients with single versus multiple metastatic lymph nodes and the role of histology in pathological stage II-N1 non-small cell lung cancer.

BACKGROUND: Previous studies investigating whether metastatic lymph node count is a relevant prognostic factor in pathological N1 non-small cell lung cancer (NSCLC), showed conflicting results. Hypothesizing that outcome may also be related to histological features, we determined the prognostic impact of single versus multiple metastatic lymph nodes in different histological subtypes for patients with stage II-N1 NSCLC. METHODS: We performed a retrospective cohort study using data from the Netherlands Cancer Registry, including patients treated with a surgical resection for stage II-N1 NSCLC (TNM 7th edition) in 2010-2016. Overall survival (OS) was assessed for patients with single (pN1a) and multiple (pN1b) metastatic nodes. Using multivariable analysis, we compared OS between pN1a and pN1b in different histological subtypes. RESULTS: After complete resection of histologically proven stage II-N1 NSCLC, 1309 patients were analyzed, comprising 871 patients with pN1a and 438 with pN1b. The median number of pathologically examined nodes (N1 + N2) was 9 (interquartile range 6-13). Five-year OS was 53% for pN1a versus 51% for pN1b. In multivariable analysis, OS was significantly different between pN1a and pN1b (HR 1.19, 95% CI 1.01-1.40). When stratifying for histology, the prognostic impact of pN1a/b was only observed in adenocarcinoma patients (HR 1.44, 95% CI 1.15-1.81). CONCLUSION: Among patients with stage II-N1 adenocarcinoma, the presence of multiple metastatic nodes had a significant impact on survival, which was not observed for other histological subtypes. If further refinement as to lymph node count will be considered for incorporation into a new staging system, evaluation of the role of histology is recommended.

Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites.

Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs and derive PDTOs from an understudied subtype of NEC, large cell neuroendocrine carcinoma (LCNEC), arising from multiple body sites. PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through hypothesis-driven drug sensitivity analyses, we identify ASCL1 as a potential biomarker for response of LCNEC to treatment with BCL-2 inhibitors. Additionally, we discover a dependency on EGF in pulmonary NET PDTOs. Consistent with these findings, we find that, in an independent cohort, approximately 50% of pulmonary NETs express EGFR. This study identifies an actionable vulnerability for a subset of pulmonary NETs, emphasizing the utility of these PDTO models.

Importance of tumour volume and histology in trimodality treatment of patients with Stage IIIA non-small cell lung cancer-results from a retrospective analysis.

OBJECTIVES: Chemoradiotherapy (CRT) has been the backbone of guideline-recommended treatment for Stage IIIA non-small cell lung cancer (NSCLC). However, in selected operable patients with a resectable tumour, good results have been achieved with trimodality treatment (TT). The objective of this bi-institutional analysis of outcomes in patients treated for Stage IIIA NSCLC was to identify particular factors supporting the role of surgery after CRT. METHODS: In a 2-centre retrospective cohort study, patients with Stage III NSCLC (seventh edition TNM) were identified and those patients with Stage IIIA who were treated with CRT or TT between January 2007 and December 2013 were selected. Patient characteristics as well as tumour parameters were evaluated in relation to outcome and whether or not these variables were predictive for the influence of treatment (TT or CRT) on outcome [overall survival (OS) or progression-free survival (PFS)]. Estimation of treatment effect on PFS and OS was performed using propensity-weighted cox regression analysis based on inverse probability weighting. RESULTS: From a database of 725 Stage III NSCLC patients, 257 Stage IIIA NSCLC patients, treated with curative intent, were analysed; 186 (72%) with cIIIA-N2 and 71 (28%) with cT3N1/cT4N0 disease. One hundred and ninety-six (76.3%) patients were treated by CRT alone (high-dose radiation with daily low-dose cisplatin) and 61 (23.7%) by TT. The unweighted data showed that TT resulted in better PFS and OS. After weighting for factors predictive of treatment assignment, patients with a large gross tumour volume (>120 cc) had better PFS when treated with TT, and patients with an adenocarcinoma treated with TT had better OS, regardless of tumour volume. CONCLUSIONS: Patients with Stage IIIA NSCLC and large tumour volume, as well as patients with adenocarcinoma, who were selected for TT, had favourable outcome compared to patients receiving CRT. This information can be used to assist multidisciplinary team decision-making and for stratifying patients in studies comparing TT and definitive CRT.

Stage I non-small cell lung cancer: Treatment modalities, Dutch daily practice and future perspectives.

OBJECTIVES: Several treatment modalities are available for patients with stage I non-small cell lung cancer (NSCLC). Over the past decade, these treatment modalities have been further investigated and might have changed current treatment regimens. In this review we present an overview of the treatment options, developments and future perspectives for stage I NSCLC. Furthermore, we describe the current use of these treatment modalities in the Netherlands. MATERIALS AND METHODS: A bibliographical search was performed in PubMed and the Cochrane Library for publications concerning treatment modalities for stage I NSCLC. In addition, evidence-based guidelines of the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) were studied. RESULTS: The guideline-recommended treatment for operable stage I NSCLC patients is a lobectomy with systematic lymph node dissection. Inoperable patients or those refusing surgery are offered stereotactic ablative radiotherapy (SABR). Percutaneous ablation, such as radiofrequency ablation, is a non-surgical minimally invasive technique offered to those who are ineligible for surgery or SABR. The role of systemic therapy is currently limited. However, the efficacy of immunotherapy is being investigated in clinical trials. In the Netherlands, an increasing use of SABR and a relative decrease in resection rates have been observed. CONCLUSION: Surgery and SABR are currently the prevailing treatment modalities for stage I NSCLC patients. Despite optimization of treatment regimens, survival of patients with stage I NSCLC remains to be improved. Future studies are required to optimize treatment strategies, but also to investigate factors influencing treatment decision-making for patients with stage I NSCLC.

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial.

IMPORTANCE: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONS: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURES: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%. CONCLUSIONS AND RELEVANCE: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02106312.

Is pneumonectomy justifiable for patients with a locoregional recurrence or persistent disease after curative intent chemoradiotherapy for locally advanced non-small cell lung cancer?

OBJECTIVES: Locoregional recurrence and persistent/progressive disease after curative-intent definitive chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is challenging to manage, as salvage options are limited. Selected patients might be candidates for resection. This study evaluated the outcomes of patients after salvage surgery for locoregional recurrence, focusing specifically on morbidity and mortality after salvage pneumonectomy. MATERIALS AND METHODS: This retrospective study included patients from 2 tertiary referral hospitals who underwent salvage pulmonary resection for locoregional recurrence or disease persistence/progression >12 weeks after completion of curative intent high dose (>60 Gy) CRT. Disease-free (DFS) and overall survival (OS) were estimated and the influence of patient and treatment characteristics on these endpoints was assessed. RESULTS: A total of 30 patients treated between 2015-2017 were identified with a median age of 60 years (range 42-72 years), 67 % were male. Median follow-up was 47 months (95 % CI 46-NR). Pneumonectomy was performed in 13/30 (43 %) patients and lobectomy in 17/30 (57 %). Median DFS and OS after pneumonectomy/lobectomy were 14/6 and NR/17 months, respectively. 30 and 90-day mortality for pneumonectomy/lobectomy were 0/12 % and 0/24 % respectively. More favorable survival was seen after pathologically radical resection, i.e. R0, and when surgery was performed more than 12 months after completion of CRT. CONCLUSION: Salvage surgery, including pneumonectomy is associated with acceptable outcomes in selected patients with recurrent or persistent/progressive NSCLC after curative-intent high dose CRT. Patients should be assessed for the probability of an R0 resection, and patients with a locoregional recurrence more than 12 months after treatment with CRT may benefit most from salvage surgery.

Results of neoadjuvant chemo(radio)therapy and resection for stage IIIA non-small cell lung cancer in The Netherlands.

Introduction: Concurrent chemoradiotherapy remains the main treatment strategy for patients with stage IIIA non-small cell lung cancer (NSCLC); stage cT3N1 or cT4N0-1 may be eligible for surgery and potentially resectable stage IIIA (N2) NSCLC for neoadjuvant therapy followed by resection. We evaluated treatment patterns and outcomes of patients with stage IIIA NSCLC in The Netherlands.Material and Methods: Primary treatment data of patients with clinically staged IIIA NSCLC between 2010 and 2016 were extracted from The Netherlands Cancer Registry. Patient characteristics were tabulated and 5-year overall survival (OS) was calculated and reported.Results: In total, 9,591 patients were diagnosed with stage IIIA NSCLC. Of these patients, 41.3% were treated with chemoradiotherapy, 11.6% by upfront surgery and 428 patients (4.5%) received neoadjuvant treatment followed by resection. The 5-year OS was 26% after chemoradiotherapy, 40% after upfront surgery and 54% after neoadjuvant treatment followed by resection. Clinical over staging was seen in 42.3% of the patients that were operated without neoadjuvant therapy.Conclusion: In The Netherlands, between 2010 and 2016, 4.5% of patients with stage IIIA NSCLC were selected for treatment with neoadjuvant therapy followed by resection. The 5-year OS in these patients exceeded 50%. However, the outcome might be overestimated due to clinical over staging.

Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma.

INTRODUCTION: Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM. METHODS: In this single-center trial, patients with MPM received nivolumab 3 mg/kg intravenously every 2 weeks. Primary endpoint was the disease control rate at 12 weeks. Pre- and on-treatment biopsy specimens were obtained to analyze biomarkers for response. RESULTS: Of the 34 patients included, 8 patients (24%) had a partial response at 12 weeks and another 8 had stable disease resulting in a disease control rate at 12 weeks of 47%. One reached a partial response at 18 weeks. In 4 patients with stable disease, the tumor remained stable for more than 6 months. Treatment-related adverse events of any grade occurred in 26 patients (76%), most commonly fatigue (29%) and pruritus (15%). Grades 3 and 4 treatment-related adverse events were reported in 9 patients (26%), with pneumonitis, gastrointestinal disorders, and laboratory disorders mostly seen. One treatment-related death was due to pneumonitis and probably initiated by concurrent amiodarone therapy. PD-L1 was expressed on tumor cells in nine samples (27%), but did not correlate with outcome. CONCLUSIONS: Single-agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pre-treated patients with mesothelioma. PD-L1 expression does not predict for response in this population.

Outcome of radical local treatment of non-small cell lung cancer patients with synchronous oligometastases.

OBJECTIVES: Patients with stage IV non-small cell lung cancer (NSCLC) are considered incurable and are mainly treated with palliative intent. This patient group has a poor overall survival (OS) and progression free survival (PFS). The purpose of this study was to investigate PFS and OS of NSCLC patients diagnosed with synchronous oligometastatic disease who underwent radical treatment of both intrathoracic disease and metastases. MATERIALS AND METHODS: Patients with NSCLC and oligometastatic disease at diagnosis, who were treated with radical intent between 2008 and 2016, were included in this observational study. Treatment consisted of systemic treatment and radical radiotherapy or resection of the intrathoracic disease. Treatment of the metastases consisted of radical or stereotactic radiotherapy, surgical resection or radiofrequency ablation. RESULTS AND CONCLUSIONS: Ninety-one patients (52% men, mean age 60 years) in good performance status were included. Thirty-eight patients (42%) died during follow-up (median follow-up 35 months). The cause of dead was lung cancer in all patients, except one. Sixty-three (69%) patients developed recurrent disease. Eleven recurrences (17%) occurred within the irradiated area. For the whole group, the median PFS was 14 months (range 2-89, 95%CI 12-16) and the median OS was 32 months (range 3-89, 95%CI 25-39). The 1- and 2-year OS rates were 85% and 58% and the 1- and 2-year PFS rates were 55% and 27%, respectively. Radical local treatment of a selected group of NSCLC patients with good performance status presenting with synchronous oligometastatic disease resulted in favorable long-term PFS and OS.

Pre- and postoperative care for stage I-III NSCLC: Which quality of care indicators are evidence-based?

Identification of evidenced-based Quality of Care (QoC) indicators for lung cancer care is essential to quality improvement. The aim of this review was to identify evidence-based quality indicators for the pre- and postoperative care of stage I-III Non Small Cell Lung Cancer (NSCLC) provided by the lung physician. To obtain these indicators, a search in PubMed, Embase and the Cochrane library database was performed. English literature published between 1980 and 2012 was included and search terms regarding 'lung neoplasms', 'quality of care', 'pathology', 'diagnostic methods', 'preoperative and postoperative treatment' were used. The potential indicators were categorized as structure, process or outcome measures and the indicators supported by literature with high evidence level were selected. Five QoC indicators were identified. The use of the positron emission tomography-computed tomography (PET-CT) results in more accurate mediastinal staging compared to the CT scan. Endoscopic Ultrasound-Fine Needle Aspiration and Endobronchial Ultrasound-Fine Needle Aspiration are sensitive diagnostic tools for mediastinal staging and reduce futile thoracotomies. Pathological conformation of lung cancer can best be obtained by a combination of cytological and histological diagnostics used during bronchoscopy. For patients with clinical stage III NSCLC, preoperative multimodality treatment (i.e. preoperative chemoradiation) results in superior survival and increased mediastinal downstaging compared to single modality treatment (i.e. preoperative chemotherapy or radiotherapy). After surgery, the addition of chemotherapy results in a significant survival benefit for patients with pathological stage II and III NSCLC. These five QoC indicators can be used for benchmarking and ultimately quality improvement of lung cancer care.

Peri- and postoperative management of stage I-III Non Small Cell Lung Cancer: Which quality of care indicators are evidence-based?

Quality of care (QoC) has a central role in our health care system. The aim of this review is to present a set of evidence-based quality indicators for the surgical treatment and postoperative management of lung cancer. A search was performed through PubMed, Embase and the Cochrane library database, including English literature, published between 1980 and 2012. Search terms regarding 'lung neoplasms', 'surgical treatment' and 'quality of care' were used. Potential QoC indicators were divided into structure, process or outcome measures and a final selection was made based upon the level of evidence. High hospital volume and surgery performed by a thoracic surgeon, were identified as important structure indicators. Sleeve resection instead of pneumonectomy and the importance of treatment within a clinical care path setting were identified as evidence-based process indicators. A symptom-based follow-up regime was identified as a new QoC indicator. These indicators can be used for registration, benchmarking and ultimately quality improvement in lung cancer surgery.

Management of large mediastinal masses: surgical and anesthesiological considerations.

Large mediastinal masses are rare, and encompass a wide variety of diseases. Regardless of the diagnosis, all large mediastinal masses may cause compression or invasion of vital structures, resulting in respiratory insufficiency or hemodynamic decompensation. Detailed preoperative preparation is a prerequisite for favorable surgical outcomes and should include preoperative multimodality imaging, with emphasis on vascular anatomy and invasive characteristics of the tumor. A multidisciplinary team should decide whether neoadjuvant therapy can be beneficial. Furthermore, the anesthesiologist has to evaluate the risk of intraoperative mediastinal mass syndrome (MMS). With adequate preoperative team planning, a safe anesthesiological and surgical strategy can be accomplished.

Tumor heterogeneity on (18)F-FDG-PET/CT for response monitoring in non-small cell lung cancer treated with erlotinib.

Response monitoring using fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography (FDG-PET/CT) textural features has potential in targeted treatment with erlotinib in non-small cell lung cancer (NSCLC) patients. Patients with substantial decrease of metabolic activity during erlotinib treatment will probably benefit from continued treatment. However, various aspects of the method (quantification tools, cut-off values, etc.) need to be standardized before the software becomes widely available in a similar manner as standardized uptake value (SUV) measurements. Heterogeneity on FDG-PET/CT opened an additional window for innovation but simultaneously a new challenge for molecular hybrid imaging.

Prognostic value of pre-operative glucose-corrected maximum standardized uptake value in patients with non-small cell lung cancer after complete surgical resection and 5-year follow-up.

INTRODUCTION: In this study we evaluated the value of pre-operative glucose corrected maximum standard uptake value (GC-SUVmax) as prognostic factor in patients with early stage non-small cell lung cancer (NSCLC) after complete surgical resection. METHODS: This study was designed as a retrospectively evaluated single center study with prospective data registry. Inclusion criteria were: histologically proven stage I NSCLC, 18F-FDG-PET/CT scan prior to surgery, complete resection (R0) and follow up in our outpatient department. Exclusion criteria were: history of malignancy other than NSCLC, diabetes and (neo) adjuvant therapy. Follow up period was 5 years. RESULTS: Between 2006 and 2008 a total of 33 patients (16 males, 17 females) met the inclusion criteria. SUVmax and GC-SUVmax were strongly correlated (Spearman's ρ = 0.97). Five-year overall survival (OS) rate was 70 % (95 % CI = 56-87 %). Patients who died within 5 years of follow up had significantly higher pre-operative GC-SUVmax (median = 10.6, IQR = 8.3-14.4) than patients who were alive at 5-year follow up (median = 6.4, IQR = 3.0-9.8), p = 0.04. SUVmax showed similar differences: 10.4 (8-12.9) vs. 6.6 (3.0-8.8), p = 0.047. The area under the receiver-operating characteristic (ROC) curve at 5 years was 0.70 (95 % CI = 0.50-0.90) for GC-SUVmax and 0.71 (95 % CI = 0.51-0.91) for SUVmax (p = 0.75). CONCLUSION: Pre-operative FDG tumor uptake in patients with NSCLC is predictive for survival after complete surgical resection. GC-SUVmax, as an additional value to SUVmax, may better approach competitive inhibition of FDG and glucose in tumors, however, in this study this potential advantage, if any, was very small.

Real-time In Vivo Tissue Characterization with Diffuse Reflectance Spectroscopy during Transthoracic Lung Biopsy: A Clinical Feasibility Study.

PURPOSE: This study presents the first in vivo real-time tissue characterization during image-guided percutaneous lung biopsies using diffuse reflectance spectroscopy (DRS) sensing at the tip of a biopsy needle with integrated optical fibers. EXPERIMENTAL DESIGN: Tissues from 21 consented patients undergoing lung cancer surgery were measured intraoperatively using the fiber-optic platform capable of assessing various physical tissue properties highly correlated to tissue architecture and composition. In addition, the method was tested for clinical use by performing DRS tissue sensing during 11 routine biopsy procedures in patients with suspected lung cancer. RESULTS: We found that water content and scattering amplitude are the primary discriminators for the transition from healthy lung tissue to tumor tissue and that the reliability of these parameters is not affected by the amount of blood at the needle tip. In the 21 patients measured intraoperatively, the water-to-scattering ratio yielded a 56% to 81% contrast difference between tumor and surrounding tissue. Analysis of the 11 image-guided lung biopsy procedures showed that the tissue diagnosis derived from DRS was diagnostically discriminant in each clinical case. CONCLUSIONS: DRS tissue sensing integrated into a biopsy needle may be a powerful new tool for biopsy guidance that can be readily used in routine diagnostic lung biopsy procedures. This approach may not only help to increase the successful biopsy yield for histopathologic analysis, but may also allow specific sampling of vital tumor tissue for genetic profiling.

Optimal surgical management of pulmonary metastases: VATS versus thoracotomy.

Survival benefit after pulmonary metastasectomy is under question and knowledge of functional recovery after pulmonary metastasectomy by thoracotomy and video-assisted thoracoscopic surgery (VATS) is of great importance. We analysed prospective data of 100 patients operated for pulmonary metastasis by either VATS or thoracotomy. VATS yielded a better physical performance 1 month postoperative, shorter hospital stay, a shorter duration of chest tube drainage and epidural analgesia. We concluded that VATS is the preferable approach due to superior functional outcome.

Concentrations of Erlotinib in Tumor Tissue and Plasma in Non-Small-Cell Lung Cancer Patients After Neoadjuvant Therapy.

INTRODUCTION: Tumors might not optimally respond to systemic therapy if minimal effective levels are not reached within the tumor. Erlotinib has mainly been studied in the adjuvant or palliative setting and, therefore, little is known about erlotinib tumor penetration. The purpose of this exploratory study was to investigate lung tumor tissue erlotinib concentrations after neoadjuvant therapy for non-small-cell lung cancer. PATIENTS AND METHODS: Patients were treated preoperatively with erlotinib (150 mg once daily for 3 weeks) up to 48 hours before surgery. Plasma samples were collected during treatment. Surgical resection involved radical resection of the lung tumor and tumor biopsies were frozen directly after surgery. Erlotinib and O-desmethyl erlotinib concentrations in lung tumor tissue and predose plasma were determined using high performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Thirteen evaluable patients were included. The mean plasma and lung tumor tissue erlotinib levels were 1222 ng/mL (SD, 678) and 149 ng/g (SD, 153), respectively. In 2 individual patients, erlotinib and O-desmethyl erlotinib concentrations in lung tumor tissue were detectable up to 13 days and 7 days after erlotinib intake, respectively. Mean erlotinib tissue concentrations extrapolated to a time point directly after intake of erlotinib were approximated at > 200 ng/g tissue, which is greater than the reported half maximal inhibitory concentration (IC50) of wild type epidermal growth factor receptor (EGFR) (183 ng/mL). CONCLUSION: No strong accumulation of erlotinib in lung tumor tissue was observed. Nevertheless, extrapolated intratumoral concentrations during erlotinib therapy were greater than the IC50 of wild type EGFR.